PMID- 27069129 OWN - NLM STAT- MEDLINE DCOM- 20160830 LR - 20220310 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 36 IP - 4 DP - 2016 Apr TI - Unfractionated Heparin Selectively Modulates the Expression of CXCL8, CCL2 and CCL5 in Endometrial Carcinoma Cells. PG - 1535-44 AB - BACKGROUND/AIM: This in vitro study analyzed the impact of heparins on expression of chemokines in human endometrial adenocarcinoma cell lines. MATERIALS AND METHODS: Cell lines were incubated with unfractionated heparin (UFH), low molecular weight heparins (LMWH) and fondparinux under hypoxic and normoxic conditions. Chemokine (C-X-C motif) ligand 8 (CXCL8), CC-chemokine ligand 2 (CCL2) and CCL5 were detected by enzyme-linked immunosorbent assays and real-time reverse transcriptase-polymerase chain reaction and cell viability by fluorometric assay. RESULTS: Different adenocarcinoma cell lines had distinct patterns of chemokine expression. UFH attenuated the secretion of CXCL8 and CCL2, and enhanced that of CCL5. The observed effects of heparin were in addition to the anti-coagulatory properties of heparin and dependent on molecular size and charge. CONCLUSION: UFH has selective modulating effects on the secretion of CXCL8, CCL2 and CCL5 in different endometrial adenocarcinoma cell lines. Molecular size and charge are relevant for these observed effects. By influencing the expression of these inflammatory mediators and thereby affecting the tumour microenvironment, heparins and related agents might play an essential role in the development of new therapeutic strategies. CI - Copyright(c) 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - Doster, Anne AU - Doster A AD - Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany. FAU - Schwarzig, Ulrike AU - Schwarzig U AD - Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany. FAU - Zygmunt, Marek AU - Zygmunt M AD - Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany. FAU - Rom, Joachim AU - Rom J AD - Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany. FAU - Schutz, Florian AU - Schutz F AD - Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany. FAU - Fluhr, Herbert AU - Fluhr H AD - Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany herbert.fluhr@med.uni-heidelberg.de. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (CCL2 protein, human) RN - 0 (CCL5 protein, human) RN - 0 (CXCL8 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Interleukin-8) RN - 0 (Polysaccharides) RN - 9005-49-6 (Heparin) RN - J177FOW5JL (Fondaparinux) SB - IM MH - Adenocarcinoma/*metabolism MH - Cell Line, Tumor MH - *Chemokine CCL2/genetics/metabolism MH - *Chemokine CCL5/genetics/metabolism MH - Endometrial Neoplasms/*metabolism MH - Female MH - Fondaparinux MH - Gene Expression Regulation, Neoplastic/drug effects MH - Heparin/*pharmacology MH - Humans MH - Hypoxia/metabolism MH - *Interleukin-8/genetics/metabolism MH - Polysaccharides/pharmacology OTO - NOTNLM OT - Heparin OT - chemokines OT - endometrial adenocarcinoma OT - tumour environment EDAT- 2016/04/14 06:00 MHDA- 2016/08/31 06:00 CRDT- 2016/04/13 06:00 PHST- 2016/01/26 00:00 [received] PHST- 2016/03/17 00:00 [accepted] PHST- 2016/04/13 06:00 [entrez] PHST- 2016/04/14 06:00 [pubmed] PHST- 2016/08/31 06:00 [medline] AID - 36/4/1535 [pii] PST - ppublish SO - Anticancer Res. 2016 Apr;36(4):1535-44.